Szakács Gergely, Annereau Jean-Philippe, Lababidi Samir, Shankavaram Uma, Arciello Angela, Bussey Kimberly J, Reinhold William, Guo Yanping, Kruh Gary D, Reimers Mark, Weinstein John N, Gottesman Michael M
Laboratory of Cell Biology, Center for Cancer Research, NCI, NIH, Bethesda, MD, 20892, USA.
Cancer Cell. 2004 Aug;6(2):129-37. doi: 10.1016/j.ccr.2004.06.026.
For analysis of multidrug resistance, a major barrier to effective cancer chemotherapy, we profiled mRNA expression of the 48 known human ABC transporters in 60 diverse cancer cell lines (the NCI-60) used by the National Cancer Institute to screen for anticancer activity. The use of real-time RT-PCR avoided artifacts commonly encountered with microarray technologies. By correlating the results with the growth inhibitory profiles of 1,429 candidate anticancer drugs tested against the cells, we identified which transporters are more likely than others to confer resistance to which agents. Unexpectedly, we also found and validated compounds whose activity is potentiated, rather than antagonized, by the MDR1 multidrug transporter. Such compounds may serve as leads for development.
为分析多药耐药性（有效癌症化疗的一个主要障碍），我们对美国国立癌症研究所用于筛选抗癌活性的60种不同癌细胞系（NCI - 60）中48种已知人类ABC转运蛋白的mRNA表达进行了分析。实时逆转录聚合酶链反应（RT - PCR）的使用避免了微阵列技术常见的假象。通过将结果与针对这些细胞测试的1429种候选抗癌药物的生长抑制谱相关联，我们确定了哪些转运蛋白比其他转运蛋白更有可能赋予对哪些药物的耐药性。出乎意料的是，我们还发现并验证了其活性被MDR1多药转运蛋白增强而非拮抗的化合物。此类化合物可能成为研发的先导物。
